{
  "abstract": "Targeting glucose metabolism in Th17 cells may be beneficial for treating inflammatory bowel disease (IBD) and colitis-associated cancer (CAC), however, the molecular mechanisms orchestrating Th17 cell metabolism remain unclear. Here, we revealed that HECTD1 regulates IGF2BP3-dependent HIF-1α translation to promote Th17 cell glycolysis and differentiation and that HECTD1 expression correlates with IBD and CAC pathogenesis. T-cell-specific deletion of HECTD1 mitigated the severity of colitis and CAC in murine models. RNA-seq revealed enrichment of Th17 differentiation, glycolysis/gluconeogenesis, and HIF-1 signaling pathways among differentially expressed genes between HECTD1-sufficient and HECTD1-deficient CD4⁺ T cells. Consistently, loss of HECTD1 suppressed Th17 cell differentiation both in vitro and in vivo, and suppressed glycolytic metabolism and HIF-1α activity, revealing the mechanism underlying its protective effects against IBD and CAC. Mechanistically, HECTD1 potentiates m⁶A-based HIF-1α translation by mediating IGF2BP3 K63-linked ubiquitination to promote the binding of IGF2BP3 with the translation initiation machinery of Hif1a mRNA. Reciprocally, HIF-1α acts as a key transcription factor that promotes Hectd1 gene expression, establishing a distinct positive feedback loop. Our findings highlight a self-reinforcing feedback mechanism in which HECTD1 and HIF-1α engage in mutual regulation to dictate Th17 cell fate and metabolic reprogramming, providing novel potential IBD and CAC treatments targeting HECTD1.",
  "abstract_shown": true,
  "affiliations": [
    "Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.",
    "Shanghai Institute of Immunology, Department of Immunology and Microbiology, State Key Laboratory of Systems Medicine for Cancer, Shanghai Jiao Tong University School of Medicine, Shanghai, China.",
    "Department of Laboratory Medicine, Institute of Laboratory Medicine, School of Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.",
    "Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.",
    "Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Shuiyu Xu"
    },
    {
      "affs": [
        1
      ],
      "name": "Qiaoqiao Han",
      "orcid": "0000-0001-9664-6532"
    },
    {
      "affs": [
        1
      ],
      "name": "Feixiang Wang"
    },
    {
      "affs": [
        2
      ],
      "name": "Yuerong Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Haoran Feng"
    },
    {
      "affs": [
        0
      ],
      "name": "Kun Liu"
    },
    {
      "affs": [
        3
      ],
      "name": "Fang Xiu Luo",
      "orcid": "0000-0003-3054-9478"
    },
    {
      "affs": [
        3
      ],
      "name": "Fei Yuan"
    },
    {
      "affs": [
        4
      ],
      "name": "Xuesong Zhao"
    },
    {
      "affs": [
        1
      ],
      "name": "Xiaoyan Yu"
    },
    {
      "affs": [
        0
      ],
      "name": "Haiyan Huang",
      "orcid": "0009-0009-5484-0084"
    },
    {
      "affs": [
        1
      ],
      "name": "Qiang Zou"
    },
    {
      "affs": [
        0
      ],
      "name": "Ren Zhao",
      "orcid": "0000-0003-1978-5912"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fg82hcpesheev.bib",
  "cited_by": 0,
  "doi": "10.1002/advs.78339",
  "fulltext_url": "https://europepmc.org/articles/PMC13677005",
  "id": "fg82hcpesheev",
  "issns": [
    "2198-3844"
  ],
  "landing_url": "https://europepmc.org/article/MED/42893454",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1311|Inflammatory Bowel Disease"
    ]
  ],
  "openalex": "W7222889258",
  "pdf_url": "https://europepmc.org/articles/PMC13677005?pdf=render",
  "pmcid": "PMC13677005",
  "pmid": "42893454",
  "published": "2026-10-18",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/fg82hcpesheev.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:46Z",
      "native_id": "MED:42893454",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42893454"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Inflammatory Bowel Disease",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "HECTD1 Directs HIF-1α to Facilitate Intestinal Inflammation and Carcinogenesis via Promoting Th17 Differentiation and Glycolysis.",
  "title_text": "HECTD1 Directs HIF-1α to Facilitate Intestinal Inflammation and Carcinogenesis via Promoting Th17 Differentiation and Glycolysis.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:46Z",
  "url": "https://research.draconitic.com/paper/fg82hcpesheev",
  "venue": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)",
  "versions": []
}